Blood Glutathione levels have been identified as being possible indicators of overall health. Glutathione, often referred to as the “master antioxidant” of the body, may have a range of diverse metabolic functions within the human body, including acting as a free radical scavenger, “recharging” depleted antioxidants back into their active state (Vitamin C, Vitamin E, Vitamin A, etc.), maintaining the immune system, supporting protein structures, promoting amino acid uptake by cells, synthesis and repair of DNA, detoxifying drugs and chemical toxins introduced to the body, removing heavy metals such as mercury, and/or other functions.
Conventional methodologies for elevating Glutathione levels include oral supplementation of Glutathione, oral supplementation of the amino acid Glutathione precursors, and use of nutritive substances that support enzymatic Glutathione production and injection of Glutathione. Each of these methods has drawbacks. For example, it is known that Glutathione may be destroyed by stomach acids making oral supplementation ineffective. While oral supplementation of amino acid precursors and Glutathione enzyme cofactors may lead to blood Glutathione levels that are elevated by 10-40% after four weeks of use, these results tend to be unpredictable, and are time- and dose-dependent. These supplements include: whey protein, selenium, lipoic acid, NAC, glutamine, glycine, vitamin C, and Vitamin E. Further, the effectiveness of supplements to improve Glutathione levels may be dependent upon many factors including patient compliance, age, level of exposure to environmental toxins, and the need to ingest the supplements multiple times during the day in order to maintain adequate Glutathione levels.
Another conventional mechanism for elevating Glutathione levels is the injection of Glutathione. The injection of Glutathione tends to translate into a temporary elevation of Glutathione levels in the blood, however, this method may be unwieldy on a daily basis. This method may also be expensive and/or inconvenient, and because of the large size of the Glutathione molecule, the injected Glutathione may be unable to penetrate the cell membrane into the interior of the cell when administered in this form. In addition, blood sampling studies of individuals given intravenous Glutathione show that blood levels of Glutathione peak in 10 minutes and are back to the baseline in 30-60 minutes. As a result, although intravenous administration of Glutathione has been proven to be somewhat beneficial in clinical studies, its use may be impractical and/or ineffective for the general population.
Despite the relative inefficiency of conventional delivery mechanisms, treatments intended to result in elevated levels of Glutathione have been shown to be effective in a variety of settings. For example, both intravenous Glutathione therapy and the use of supplements that increase Glutathione levels have been shown to be effective in alleviating the symptoms of Parkinson's disease.
Glutathione levels have been shown to be reduced in diabetics and Glutathione metabolism is impaired by diabetes. Poorly controlled diabetics, who have depleted Glutathione, also show an evident impairment of glucose metabolism and a higher susceptibility to oxidative injury. In these subjects, the effect of exogenous Glutathione is more noticeable than in those with near-normal blood glucose. Treatments that increase Glutathione levels are also associated with better blood sugar control in diabetics as well as less diabetic complications. As a result, intravenous Glutathione is now being used as one method of treatment for diabetes.
As another example, intravenous Glutathione has been shown to be helpful in reducing exercise-related pain in individuals with peripheral artery disease.
Glutathione levels in the brain are reduced by use of thiomersal, a mercury containing substance placed in some vaccines. Some researchers believe that the acute depletion of Glutathione by mercury containing compounds in vaccines creates neurotoxicity. The severity of the illness may be related to the total amount of mercury received and the time-frame of the exposure. A number of studies have now confirmed that autistic children have reduced circulating levels of Glutathione in their blood stream and laboratory markers indicating increased oxidative stress. Tremendous controversy exists about this issue, with many doctors and parents now believing that vaccines containing this substance, along with other sources of mercury exposure, may cause autism. Both intravenous Glutathione therapy and oral antioxidant substances are widely used by many clinicians around the world in the treatment of autism because of the clinical results produced when these therapies are given. The reason Glutathione is used to treat mercury toxicity is because Glutathione is the major mechanism used by the liver, kidneys and brain to excrete mercury.
Medical literature demonstrates that various pharmaceutical chemicals and drugs deplete Glutathione levels in the body. In 1993 it was reported that 200-300 deaths occurred every year from acetaminophen poisoning in the UK. In the USA overdoses of prescription and nonprescription drugs containing acetaminophen results in more calls to poison control centers in the US than do overdoses of any other medication, accounting for more than 100,000 calls, as well as 56,000 emergency room visits, and 458 deaths due to acute liver failure per year. A report on the cases acute liver failure by the CDC between 2000 and 2004 determined that acetaminophen toxicity was the cause in 41% of adult cases of liver failure. The reason for the deaths from acute liver failure after acetaminophen overdose results from acute depletion of liver Glutathione levels. Glutathione is a critical antioxidant molecule involved in the detoxification of acetaminophen in the liver. If a person does not receive immediate treatment with Glutathione producing substances, the liver will fail and then the only other treatment is a liver transplant. The acute treatment of poisoning with this analgesic involves using antidotes such as intravenous infusions of N-acetylcysteine or alpha-lipoic acid, which are nutrients used by the body to produce Glutathione.
In 1977, Dr. Burton M. Berkson also discovered that alpha-lipoic acid, which generates Glutathione production in the liver, could also save the livers of individuals suffering from mushroom poisoning. Similarly, mild cases of liver toxicity are often treated with oral doses of N-acetylcysteine, alpha-lipoic acid or the essential amino acid methionine, which serve as substrates for Glutathione synthesis in the body.
In addition, the use of Glutathione promoting compounds, like alpha-lipoic acid along with silymarin and selenium, can be beneficial in some individuals suffering from viral hepatitis because of their ability to regenerate antioxidants and protect the liver from free-radical damage.
Drugs commonly used in anesthesia practice may create oxidative stress and Glutathione depletion in peripheral T cells. This supports Glutathione levels in individuals who are undergoing surgical procedures where anesthetic agents are used. In addition, maintaining Glutathione levels in individuals who are recovering from injuries and surgery is beneficial because of the positive response that Glutathione has on wound healing.
Glutathione may be beneficial in controlling side-effects associated with cancer therapies. For instance, non-prescription antioxidants and other nutrients may enhance the killing of therapeutic modalities for cancer, decrease their side effects, and protect normal tissue. Glutathione treatment has been shown to be an effective in reducing toxicity and side effects in individuals with ovarian cancer who are treated with cisplatin chemotherapy. More particularly, treatment with Glutathione has been shown to improve patients conditions with respect to depression, emesis, peripheral neurotoxicity, hair loss, shortness of breath and difficulty concentrating. As another example, many individuals will develop neurological symptoms when given chemotherapy agents. Some studies have shown that chemotherapy agents lower Glutathione levels in brain tissue and that the use of Glutathione can reduce brain toxicity, which may be associated with these neurological symptoms.
Another bodily system that appears to benefit from elevated Glutathione levels is the immune system. This may be in part because infections generally tend to deplete Glutathione levels in the body. The immune system works best if the lymphoid cells have adequate levels of Glutathione. Even small reductions in the intracellular Glutathione level may have effects on lymphocyte and immune functions. Rheumatoid arthritis and systemic lupus erythematosus are two chronic inflammatory conditions linked with the immune system, which have been associated with low levels of serum and erythrocyte Glutathione when compared to normal. Glutathione levels as measured by erythrocyte Glutathione are also low in the blood of individuals with osteoarthritis.
Glutathione is involved in T-cell activation low, and Glutathione could affect the outcome of the immune response during systemic diseases and aging. Because Glutathione depletion may occur in conjunction with sepsis, trauma, and shock, treatments that help maintain Glutathione levels may enhance immunocompetence and thus improve the ability of patients to recover from these and other critical illnesses.
Similarly, inflammation (e.g., due to infection and/or trauma) may suppress Glutathione levels, and/or present a variety of other health risks. For instance, when inflammation is prolonged, tissue damage, enhanced inflammatory mediator production, and suppressed lymphocyte function may occur as a consequence. In addition, chronic inflammation may predispose susceptible cells to undergo cancerous transformation. In general, the longer the inflammation persists, the higher the risk of cancer. Inflammatory processes may induce DNA mutations in cells via oxidative stress. DNA mutation and mitochondrial dysfunction occurs when the generation of free radicals in a system exceeds the system's antioxidant protection.
Reduced Glutathione levels have also been linked to various viral diseases. This may be at least in part because Glutathione levels tend to fall when a virus infects cells. Increasing the levels of Glutathione inhibits viral replication and can reduce viral load. Reduction of viral load with use of Glutathione has been seen in herpes infections, hepatitis viral infections, and HIV infections. Viral infections produce oxidative stress by depleting Glutathione levels. Clinical studies have indicated that antioxidant therapies that increase Glutathione can assist the body in dealing with infections. For example, Glutathione levels dramatically decrease in the first 24 hours after infection with human herpes simplex virus type 1 (HSV-1). Antioxidant molecules, such as GSH and N-acetylcysteine (NAC), have been demonstrated to inhibit viral replication. Similarly, antioxidant molecules to inhibit >99% the replication of HSV-1. Such inhibition may be concentration-dependent, not related to toxic effects on host cells and also maintained if the exogenous GSH is added as late as 24 hours after virus challenge, i.e., when virus infection has been fully established. As another example, N-acetylcysteine (NAC), a sulfur-containing amino acid antioxidant, appears to inhibit HIV replication by raising serum Glutathione levels through inhibition of TNF-a [Tumor Necrosis Factor]. In chronic hepatitis C, liver damage may be attributed to increased oxidative stress and Glutathione depletion. Use of therapies that increase Glutathione levels like NAC have shown clinical benefit.
An imbalance in oxidant/antioxidant levels in the cells and tissues is a major cause of cell damage and is the hallmark for lung inflammation. Glutathione is a vital protective antioxidant, which plays a key role in the control of inflammatory processes in the lungs. Oxidative stress is an important feature in the causation of chronic obstructive pulmonary disease. Controlling oxidative stress with antioxidants or boosting the endogenous levels of antioxidants such as Glutathione is likely to be beneficial in the treatment of chronic obstructive pulmonary disease.
The role of oxidative stress in acute pancreatitis has been evidenced indirectly by beneficial effects of antioxidants as well as directly by pancreatic Glutathione depletion and increased lipid peroxidation.
In burn patients, increased free radical production is paralleled by impaired antioxidant mechanisms, as indicated by burn-related decreases in superoxide dismutase, catalase, Glutathione, alpha tocopherol, and ascorbic acid levels. This supports the hypothesis that cellular oxidative stress is a critical step in burn-mediated injury, and suggests that antioxidant strategies designed to inhibit free radical formation and/or to scavenge free radicals may provide organ protection in patients with burn injury.
Acute strokes and acute myocardial infarctions create severe oxidative stress on the body. The body will initially respond adaptively by increasing the production of antioxidant enzymes like Glutathione in order to protect and preserve surviving tissues. This places severe demands on the production of antioxidants like Glutathione. If and when the demands overwhelm the production of endogenous antioxidants like Glutathione, antioxidant levels including Glutathione levels fall, and tissue damage becomes more severe. This may be particularly critical in the first week following an ischemic event when antioxidant enzyme concentrations are decreased below normal levels. Maintaining adequate levels of antioxidants in individuals with vascular disease and in individuals who have ischemic events can help reduce medical complications.
Glutathione levels fall with age, and older individuals in good health tend to have higher Glutathione levels. The reduction in antioxidant protection associated with reduced levels of Glutathione has been implicated in the increasing susceptibility to carcinogens, infections, disease, and drug sensitivity which occurs with advanced age.
During warfare, soldiers (and/or civilians) may be exposed to various toxic substances. Treatment intended to increase Glutathione levels may be beneficial to counteract the effects of these exposures. For example, organofluoride polymers are considered important and are used extensively in military vehicles such as tanks and aircraft. The occurrence of closed-space fires in such settings has led to toxicity studies of the resultant by-products created from incinerated organofluorines. Inhalation of a mixture of pyrolysis by-products of these substances produces a constellation of symptoms termed “polymer fume fever” Inhalation of this material may produce a “permeability” or “noncardiac” type of toxic pulmonary edema very much like that produced by phosgene. Animal studies suggest that increasing pulmonary concentrations of oxygen free-radical scavengers like Glutathione may be of value in counteracting these and other effects of this type of exposure. For example, N-acetyl cysteine has been found effective in increasing Glutathione levels. Similarly, effects of weaponized chemical agents, such as mustard gas, phosgene, and/or other agents, may be treated by elevating Glutathione levels.
Strenuous and prolonged exercise can deplete antioxidants including Glutathione in the body. Prolonged or repetitive aerobic activity causes the body to utilize large amounts of oxygen to produce ATP in the mitochondria. Unfortunately, oxygen utilization in the mitochondria also produces significant amounts of oxygen free radicals. A higher amount of exercise unavoidably produces larger amounts of free-radicals that must be neutralized by the body's antioxidant systems. The body can compensate for strenuous exercise by increasing antioxidant enzyme activity up to a point. However, prolonged, intensive and repetitive bouts of exhaustive exercise can eventually overwhelm the body's antioxidant reserves. When the antioxidant system begins to fail continuous oxidative stress can eventually overwhelm the protective mechanisms leading to impairment in cellular functions such as energy production and impairment of liver detoxification. Clinical research in animals has shown that when strenuous exercise is continued after Glutathione depletion has occurred, oxidative damage can be seen in the liver and endurance is significantly decreased. Physical exercise also may significantly increase total oxygen uptake by the body by 1000-2000%; however, oxygen flux in skeletal muscle fibers may increase by as much as 100- to 200-fold during exercise; generating massive amounts of reactive oxidant species.
If the generation of reactive oxygen species during physical exercise overwhelms tissue antioxidant defense systems then antioxidant levels may reach a state of depletion. Although an oxidant insult may lead to adaptive responses and strengthen antioxidant defenses in the heart and skeletal muscle tissue. Oxidative stress, however, can also lead to cardiac and skeletal muscle tissue damage in individuals who are not able to upregulate their antioxidant defense mechanisms. The levels of oxidized Glutathione rise during strenuous exercise, as Glutathione is used up in the tissues. Unless Glutathione is regenerated back to its active reduced state, free radicals will attack vulnerable cellular structures like cell membranes, which can be monitored by measuring the amount of lipid peroxidation in both blood and urine. Maintaining high blood Glutathione levels are associated with lower resting, and exercise-induced, lipid peroxidation. In humans, exercise-induced blood Glutathione oxidation is rapid and subject to control by antioxidant supplementation. Antioxidant supplementation is likely to provide beneficial effects against exercise-induced oxidative tissue damage.
Hearing loss due to exposure to high-levels of sound and noise is a problem for many people in all walks of life. People who listen to music with ear plugs, loud rock concerts, factory workers and military personnel are all subject to hearing loss due to high levels of sound and noise. Research has shown that noise and loud sounds will deplete Glutathione levels in ear cells and will lead to hearing loss and that therapies that maintain Glutathione functional levels in the ear cells will protect against hearing loss. One factor that has been identified is that exposure to noise will produce autotoxic free radicals, Glutathione depletion within the sensory hair cells, and Glutathione depletion in the bloodstream. The generation of free radicals by high-level noise and Glutathione depletion is thought to be one of the mechanisms involved in producing noise-induced-hearing-loss (NIHL).
Although sensory hair cells possess a natural antioxidant defense system involving Glutathione and Glutathione regenerating enzymes that neutralize free radicals, this system can become overwhelmed in extreme or chronic noise conditions or by exposure to certain types of drugs or toxins. Exposure to high-level noise and certain ototoxic drugs can damage cellular structures in sensory hair cells like cell membranes, proteins, mitochondria and DNA when the rate of generation of cytotoxic free radicals exceeds the neutralization capabilities of the antioxidant system. When the cell membrane is damaged, the cells cannot properly maintain their electrical potentials, nutrient entry, and toxin release. The cell membrane is primarily composed of phopholipids and sterols. These compounds are synthesized from precursors provided by the diet. Both cell membranes and cell organelles are often damaged by oxidative processes and need continual protection from antioxidant defenses and a continual source of cellular energy, which is obtained from high-energy phosphates produced by metabolic energy pathways. Metabolic and antioxidant pathways operate through membrane-associated enzymes that require nutrient precursors and vitamin and mineral enzyme activators.
Other benefits may be associated with enhanced levels of Glutathione.